Additional Insights: Management of Ibrutinib in CLL

EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Kristen Battiato, AGNP-C: The long-term follow-up on the RESONATE-3 trial, which compared ibrutinib to ofatumumab, showed that ibrutinib is far superior to ofatumumab. Patients who were on ibrutinib for prolonged periods achieved a deep and durable response. However, there is a small population of patients who are intolerant to ibrutinib, and they have to come off due to intolerance. Certain toxicities associated with ibrutinib include fatigue, diarrhea, headache, arthralgias and myalgias, hypertension, and atrial fibrillation.

Most commonly these toxicities can occur within the first 6 to 12 months of initiating therapy with ibrutinib. Hypertension is one of the toxicities that has a cumulative effect that can occur a little later.

It’s something that we have to continually monitor for, especially people on ibrutinib for prolonged periods.

It’s really important to follow the FDA label with monitoring patients for toxicities related to ibrutinib. There are certain ways we’ve managed patients with ibrutinib toxicity. The first way is sometimes, depending on how severe their toxicity is, we’ll hold the drug for a small period of time, meaning 1 to 2 weeks, and we’ll re-challenge the patient. Additionally, we can dose reduce, depending on how severe their toxicities are.

Thirty percent to 40% of patients on ibrutinib will experience some kind of toxicity; 10% to 15% of those patients will actually have to come off therapy due to these toxicities.

Depending on what the patient is experiencing, if it’s manageable or tolerable, we will try symptom support. If it’s severe, we will have a discussion with the attending physician and determine whether the patient will need to stop the drug either temporarily or permanently, or if it can be managed symptomatically.

Depending on the toxicity the patient is experiencing, if they are having diarrhea, for instance, we could try Imodium, increase fluid intake, and amend the diet to simple, bland foods, following the BRAT [bananas, rice, applesauce, toast] diet. If someone is experiencing hypertension, we could add an antihypertensive agent and involve cardiology. So, it depends on the toxicity and how severe it is.

I typically educate patients when starting ibrutinib to report any new symptoms, whether it be diarrhea, headaches, any new rashes or bleeding that may occur. In addition, I stress it’s really important to report any lightheadedness, chest pain, or palpitations, to make sure we’re not missing an arrhythmia, such as atrial fibrillation or atrial flutter. It’s important also to report any kind of procedures that they may be having, surgical procedures especially, because we’ll have to hold the drug 3 to 7 days before and after the procedure. We also note the importance of medication compliance. It’s important to take it correctly and around the same time every day.

We typically monitor the patient starting ibrutinib therapy with weekly laboratory tests during the first month. We look for tumor lysis labs along with a CBC [complete blood count]. In addition to that, we’ll check in with them occasionally just to make sure they’re tolerating the drug OK and they’re being compliant. After that, we’ll have a check-in visit typically 1 month after starting therapy. Depending on how they’re tolerating the medication, we’ll then decide a follow-up schedule with them. We typically see patients at least every 3 months who are on therapy with ibrutinib.

It’s really important to follow the FDA label for guidance in managing toxicities with ibrutinib. The label is extremely helpful with guidance on dose reduction and symptom management. Not every adverse effect is attributable to ibrutinib, meaning patients have other comorbidities and they have to be taken into account as well.

Also, it’s important to utilize the multidisciplinary team. Patients may require cardiology consults, infectious disease, dermatology, the important use of primary care and keeping up with preventive screenings, those are really important. Also, utilizing pharmacy for potential drug interactions in addition to the office practice nurses and advanced practice nurses or APPs [advanced practice providers]. It’s important to encourage open dialogue with your patients, whether it be the patient portal or contacting the office. They have to be comfortable with communicating adverse effects and checking in and how they’re feeling. That’s really important.

Patients diagnosed with CLL have a lot more treatment options than previously. Chemotherapy is no longer the sole therapy available to them. These targeted novel agents provide a better toxicity profile, they’re well-tolerated, and they’re very active for people, especially with high-risk disease. There are also a lot of exciting clinical trials right now going on that will hopefully provide even more treatment options in the future, so patients have a lot of treatment options and hopefully will have better outcomes.

Transcript edited for clarity.